Support is requested for a Keystone Symposia meeting entitled Fibrosis: From Basic Mechanisms to Targeted Therapies, organized by Robert Lafyatis, Paolo G.V. Martini, Dean Sheppard and Lucie Peduto. The meeting will be held in Keystone, Colorado from February 7-11, 2016. Fibrosis is the primary process of many diseases and the end-stage of many more, frequently leading to organ failure. However, the mechanisms leading to fibrosis have been poorly understood and available therapeutics targeting fibrosis limited. Increasingly, fibrosis is understood as a dynamic process that is orchestrated by the immune system, or activated by inflammation or cellular stress. Fibrosis of lung, kidney, skin, liver and muscle typically follow a variety of different stimuli. Advances in understanding Th2 cell responses, cell death, the inflammasome and ER and oxidative stresses provide new insights into such stimuli. Understanding the regulation of, and interaction between, profibrotic cytokines such as TGFb, IL-13, and CTGF are shedding additional light on fibrotic processes. Recent studies indicate that fibrosis is mediated by dedicated progenitor and resident cells within target tissues. Fibroblast and perivascular cell phenotype and differentiatio are regulated not only by cytokines, but also by matrix composition and stiffness. Advances in the treatment of idiopathic pulmonary fibrosis and systemic sclerosis herald many new anti-fibrotic therapies that will soon enter clinical trials. Thus, mechanistic understandings will soon answer the long-standing clinical challenges of fibrotic and end-stage scarring diseases. Thus, this meeting addresses an important public health challenge relevant to the NHLBI mission. Specifically, fibrosis is the end stage and life-threatening complication of most interstitial lung diseases, affecting many adults and children. Current treatments for fibrotic lun disease are extremely limited, so it continues to represent a major national health problem. The most common form of pulmonary fibrosis, Idiopathic Pulmonary Fibrosis (IPF), has a prevalence in the US of between 28 and 63/100,000 depending on whether narrow or more broad criteria are used for case definition. Current estimates are that the mean survival is 3 years from the time of diagnosis. The prevalence of pulmonary fibrosis from all causes is probably 3 times higher than the prevalence of IPF.